Special Report: Do Psych Drugs Do More Long-Term Harm Than Good?

It was an explosive question: Might it be that the overuse of psychiatric medications is making many people sicker than they would have been, and preventing their recovery? Are the medications causing an epidemic of long-term psychiatric disability?

And it was about to be debated at a pinnacle of psychopharmacology, the top-rated psychiatry department in the country.

The match had drawn a full house to the fabled “Ether Dome” at Massachusetts General Hospital, the historic medical amphitheater where ether was first demonstrated as an anesthetic in 1846.

Against a vintage backdrop of glass cases holding a mummy and a well-used skeleton, the two adversaries were about to engage in a “grand rounds” debate — academic medicine’s intellectual equivalent of hand-to-hand combat.

"Thank you," Massachusetts General Hospital psychiatrist Andrew Nierenberg said wryly, "for coming to the belly of the beast."

The question is, author Robert Whitaker responded just as wryly, "Will I survive?"

End of humor. The stakes were too high for jokes. In his new book, “Anatomy of an Epidemic,” Whitaker doesn't just ask whether long-term medication might often do harm. He presents study after mainstream study that inform his thesis, and he calls for the psychiatry establishment to discuss it openly.

'The 'Silent Spring' of Psychiatry?

A science journalism maven at Harvard told me recently, "Mark my words, this book is going to be the 'SIlent Spring' of psychiatry" — a reference to the classic Rachel Carson book that opened the country's eyes to the harmful effects of DDT.

“Anatomy of an Epidemic” only came out in April; it remains to be seen how widely its ripples will spread. But one thing is already clear: It has set Bob Whitaker, an award-winning local journalist and author of four books, on a personal journey into unexplored territory, to the Ether Dome and beyond.

It is taking him to a national conference on his hypothesis led by psychiatrists and providers of mental health services in Oregon next month. And to a line-crossing move for any journalist: the founding of a non-profit,“The Foundation for Excellence in Mental Health Care,” that will aim to present the science on various psychiatric treatments in a clear and unbiased way.

Most recently, that journey led him last week to stand in the Ether Dome beneath the curved rows of stadium-style seats, speaking upward to the full audience. Most of his listeners looked like students, except for a cluster of older men in the front whose bow-ties or suits gave them the look of staff.

Looking up at the Ether Dome

As the psychiatry establishment goes, this truly was "the belly of the beast": Massachusetts General's psychiatry is consistently ranked as the top department in the country by U.S. News and World Report. Sitting at the very front in a dark navy sweater was Jerrold Rosenbaum, the department chair.

Whitaker began with the plot-line about psychiatric drugs that tends to dominate in American society: The introduction of Thorazine in 1955 kicked off a “psychopharmacological revolution” that has included a march of new antipsychotics and antidepressants that are “sort of antidotes to these disorders.” They make it possible to empty institutions, and prevent people from becoming chronically ill. All in all, a positive picture of progress.

Troubling questions

Except that there’s a troubling puzzle: Why, then, did the number of Americans on the disability rolls for mental health reasons triple between 1987 and 2007?

And more troubling questions: Yes, the drugs often help people short-term, and sometimes, longer term. But why do some data suggest that schizophrenics who take anti-psychotics fare worse, long-term, than those who don’t? Why do so many people with depression who take anti-depressants seem to flip into bipolar disorder? And why is the disability caused by bipolar disorder rising so sharply, anyway?

Two of the studies that Whitaker described were particularly striking:

A World Health Organization study [here] found that schizophrenia patients living in poor countries did better long-term than schizophrenics in rich countries. In fact, “Living in a developed country is a strong predictor that a person will never recover from schizophrenia,” he told the audience. “That actually was the study that got me interested in this whole question from the start.”

And a study of 145 psychotic patients over 15 years [here] found that among those who took antipsychotics, only 5% recovered, compared to 40% of those who were off the drugs.

Yes, there could be confounding factors; certainly, patients who were doing better were likelier to go off the drugs. But “I think history is telling you this story,” Whitaker said. “With first-episode patients, you actually want to delay using anti-psychotics, because a significant percentage will get better without needing to go on the drugs, and long-term, you want to try to get as many people off as possible.” A group in Finland began using the medications in that selective way in 1992, he said, and to great success. [That study is here.]

“I don’t think that’s an anti-medication story,” he said. “I think it’s a best-use-of-medication story.”

The refutation

Dr. Andrew A. Nierenberg, director of Mass. General’s bipolar research program and a Harvard professor of psychiatry, disagreed.

“I’m going to refute much of what you said,” he warned after he took over the podium.

In particular, he challenged Whitaker’s numbers on the dramatic rise in the disability rolls, pointing out that according to epidemiological studies, the prevalence of mental illness has remained roughly the same in recent decades. Disability rates, he said, remained similarly stable — even as far more people sought treatment.

“If anything,” he allowed, “We’re realizing over time that our medications don’t work as well as we would like them to in some ways, but I also would assert that it doesn’t cause the amount of harm asserted in the book.”

Getting it 'backwards'

Nierenberg also directly challenged the 15-year study of schizophrenics. The study's author himself stated that his findings could be interpreted as meaning that "People who had been doing better said, ‘I don’t want to take this anymore’ and stopped,” he said. To claim that the people did better because they were off medications, he said, ‘is backward.”

As for schizophrenia in poor countries, Nierenberg said, consider a two-year epidemiological study of outcomes among 510 schizophrenics in China. Those who got no treatment did worse in every category than those who did receive treatment, he said.

More: Other longitudinal research that used sophisticated analyses to adjust for the severity of the disorder shows, he said, that among thousands of episodes of depression, patients who got treatment virtually doubled their odds of getting better and cut in half their odds of getting depressed again. And in a half-dozen studies, the longer psychosis went untreated, the worse the outcomes, he said.

The rhetoric ramped up. Nierenberg also accused Whitaker of “gratuitous and misinformed attacks” on the pharmaceutical industry and academia; of denying that mental illness and psychiatry have a biological basis; and of “omitting contradictory data.” Also, “faulty and simplistic reasoning” that “confuses cause and effect.” He said Whitaker “misinterprets outcome studies and comes up with wrong conclusions that end up an indictment of psychopharmacology.”

'This book contains misinformation'

“The book should have a warning label,” he said: “This book contains misinformation.”
We have, he concluded, “a profound disagreement about the data and what it shows.”

Whitaker riposted on several of Nierenberg’s points. On biology, Whitaker said, “It’s not that I don’t believe there are biological causes involved; what I don’t believe is that these drugs ‘fix’ a known chemical imbalance.”

On the Chinese study, he said, the study was skewed because some of its subjects had already been ill for ten years; and “No one is saying that no treatment is a desirable thing. The question is what treatment.”

On depression, Whitaker said, in fact, the untreated group had milder, shorter episodes and one-third the rate of disability of the treated group.

Public trust

As he concluded, Whitaker’s own rhetoric ramped up: “Why do we, as a society, believe that these drugs fix chemical imbalances?” Why do we believe new drugs are better than older ones? “What are the storytelling forces in our society and who do we trust as a population to give us the honest truth? We believe in academic psychiatry,” he said. “We want you to be the arbiters of honest information.” Yet, he said, new drugs get hyped; studies showing negative results don’t get published.

“My appeal here is that we need an honest discussion of the data,” he said. “You’re right,” he told Nierenberg. The end of the book did hold an indictment: “I don’t think academic psychiatry, which had that trust, has honored that trust and been fully open with the public.”

The chief's belief

No punches pulled. But the hour-long session ended on a conciliatory note. Department chair Jerrold Rosenbaum noted that “We were the place that first began to highlight the risks of treatment discontinuation” — in which patients’ symptoms flare up when they try to go off a drug — “and how to sort that out from relapse. We had our share of criticism from industry and colleagues, and this is still an important question.”

“My belief,” he continued, “is that there are some people for whom Bob’s hypothesis is probably true, and others for whom it’s not, and our challenge is to learn enough about the biology of the disease, the genetic propensities, and be able to predict and match treatments to those patients so we get it right.”

The last word went to Marlene Freeman, an associate professor of psychiatry in the audience. "Most of us are humbled by what we do every day," she said. "We do our best to give our patients the most accurate risk-benefit analyses of treatment choices."

Well-designed studies to really answer the questions you raise are very expensive, she told Whitaker. If you could take some of your passion to the National Institute of Mental Health and get them to fund some of them, “We’d be very grateful.”

Actually, the very last word goes to yours truly. My verdict is that both sides came away bloodied but unbowed. And that I’m very happy that Bob Whitaker is getting his wish for open discussion. The public discourse about psychiatry tends to be polarized, tainted by drug-company money or by extreme anti-psychiatry views that paint practitioners as evil villains. The debate that Whitaker is raising may be full of arguments with sharp bite, but it sounds well-meaning and rational.

When I read his “Anatomy of an Epidemic,” I found it highly persuasive — persuasive enough to make me significantly more wary of psychiatric medications — but still just the beginning of a discussion that needs more data to feed it. Judging by the response at the Ether Dome, that debate may be a lively one for a long time.

Whitaker will likely have a role with the new Foundation For Excellence in Mental Health Care, he said, so he may have to give up writing about psychiatry as a journalist. But perhaps he’ll be able to chronicle a transformation in psychiatry toward better long-term outcomes.

“I don’t want to give up writing,” he said. But “if you do have a book that seems to be making an impact, and you do think it’s an important subject that affects lives, you sort of have to go with that.”

Recently, I had the chance to read a beautifully written essay by an MIT student who had been hospitalized, diagnosed with bipolar disorder, and prescribed a variety of drugs that, he writes, caused side effects ranging from kidney problems to extreme paranoia to a general deadening of his curiosity and creativity. When he came upon "Anatomy of an Epidemic," he writes:

I didn't think much of it upon first inspection, but ended up reading the entire thing in one sitting. For the first time, I was seeing a thoroughly-researched collection of studies that vindicated my personal experience. I saw dozens of charts, each with at least one data point dedicated to me. The long-term effects of psychotropic drugs were, I learned, largely unknown. This had been mentioned to me in the past, but always as an aside. Whitaker's message seemed clear and convincing: psychiatric drugs do seem to have a purpose for specific cases, but the current practice of "long-term treatment" may have consequences that do significant harm to the patient.

Readers, your thoughts and questions on this topic are deeply welcome in the comments section. And you can listen to Radio Boston's recent segment with Whitaker and Nierenberg here.

(A 2011 Favorite)

This program aired on January 19, 2011. The audio for this program is not available.

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Carey Goldberg Editor, CommonHealth
Carey Goldberg is the editor of WBUR's CommonHealth section.



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